Oxidative Stress Profile Research Articles

Effect of silver nanoparticles on cytotoxicity, oxidative stress and pro-inflammatory proteins profile in lung adenocarcinoma A549 cells.

The general population is exposed to silver nanoparticles (AgNPs) released into the environment, e.g. through the respiratory tract. Lung cancers are among the most frequently diagnosed and deadly malignancies, often diagnosed at late stage with existing distant metastases. The aim of the study was to determine the activity of AgNPs against A549 lung cancer cells. A549 cells and AgNPs were used in the study. Cytotoxicity was tested by MTT and NR assays. Oxidative stress was determined by measuring malonyldialdehyde and level of free -SH groups Proteins secretion was assessed using the Human Profiler Cytokine Array Kit assay. AgNPs reduce A549 cells viability and induce oxidative stress. They also lead to increased secretion of several proinflammatory proteins, which stimulate metastasis. AgNPs exhibit direct anti-cancer effect, however, their potentially promethastic effect encourages further work on the safety of nanomaterials.

Stress responses to warming in Japanese flounder (Paralichthys olivaceus) from different environmental scenarios

Japanese flounder (Paralichthys olivaceus) is one of cold-water species widely farmed in Asia. In recent years, the increased frequency of extreme weather events caused by global warming has led to serious impact on Japanese flounder. Therefore, it is crucial to understand the effects of representative coastal economic fish under increasing water temperature. In this study, we investigated the histological and apoptosis responses, oxidative stress and transcriptomic profile in the liver of Japanese flounder exposed to gradual temperature rise (GTR) and abrupt temperature rise (ATR). The histological results showed liver cells in ATR group were the most serious in all three groups including vacuolar degeneration and inflammatory infiltration, and had more apoptosis cells than GTR group detected by TUNEL staining. These further indicated ATR stress caused more severe damage than GTR stress. Compared with control group, the biochemical analysis showed significantly changes in two kinds of heat stress, including GPT, GOT and D-Glc in serum, ATPase, Glycogen, TG, TC, ROS, SOD and CAT in liver. In addition, the RNA-Seq was used to analyze the response mechanism in Japanese flounder liver after heat stress. A total of 313 and 644 differentially expressed genes (DEGs) were identified in GTR and ATR groups, respectively. Further pathway enrichment of these DEGs revealed that heat stress affected cell cycle, protein processing and transportation, DNA replication and other biological processes. Notably, protein processing pathway in the endoplasmic reticulum (ER) was enriched significantly in KEGG and GSEA enrichment analysis, and the expression of ATF4 and JNK was significantly up-regulated in both GTR and ATR groups, while CHOP and TRAF2 were high expressed in GTR and ATR groups, respectively. In conclusion, heat stress could cause tissue damage, inflammation, oxidative stress and ER stress in the liver of Japanese flounder. The present study would provide insight into the reference for the adaptive mechanisms of economic fish in face of increasing water temperature caused by global warming.

Effect of diets enriched in n-6 or n-3 fatty acids on dry matter intake, energy balance, oxidative stress, and milk fat profile of transition cows

The objective of this study was to determine the effect of dietary supplementation of n-3 polyunsaturated fatty acids (PUFA) and n-6 PUFA on dry matter intake (DMI), energy balance, oxidative stress, and performance of transition cows. Forty-five multiparous Holstein dairy cows with similar parity, body weight (BW), body condition score (BCS), and milk yield were used in a completely randomized design during a 56-d experimental period including 28 d prepartum and 28 d postpartum. At 240 d of pregnancy, cows were randomly assigned to one of the 3 isoenergetic and isoprotein dietary treatments, including a control ration containing 1% hydrogenated fatty acid (CON), a ration with 8% extruded soybean (HN6, high n-6 PUFA source), and a ration with 3.5% extruded flaxseed (HN3; high n-3 PUFA source). The HN6 and HN3 diets had an n-6/n-3 ratio of 3.05:1 and 0.64:1 in prepartum cows and 8.16:1 and 1.59:1 in postpartum cows, respectively. During the prepartum period (3, 2, and 1 wk before calving), DMI, DMI per unit of BW, total net energy intake, and net energy balance were higher in the HN3 than in the CON and NH6 groups. During the postpartum period (2, 3, and 4 wk after calving), cows fed HN3 and HN6 diets both showed increasing DMI, DMI as a percentage of BW, and total net energy intake compared with those fed the CON diet. The BW of calves in the HN3 group was 12.91% higher than those in the CON group. Yield and nutrient composition of colostrum (first milking after calving) were not affected by HN6 or HN3 but milk yield from 1 to 4 wk of milking was significantly improved compared with CON. During the transition period, BW, BCS, and BCS changes were not affected. Cows fed the HN6 diet had a higher plasma NEFA concentration compared with the CON cows during the prepartum period. Feeding HN3 reduced the proportion of de novo fatty acids and increased the proportion of preformed long-chain fatty acids in regular milk. In addition, the n-3 PUFA-enriched diet reduced the n-6/n-3 PUFA ratio in milk. In conclusion, increasing the n-3 fatty acids concentration in the diet increased both DMI during the transition period and milk production after calving, and supplementing n-3 fatty acids was more effective in mitigating the net energy balance after calving.

CARDIOPROTECTIVE EFFECT OF TERIFLUNOMIDE IN AN EXPERIMENTAL MODEL OF MYOCARDIAL INFARCTION

Objective: MI is a major cause of mortality worldwide. Inflammation plays a key role in the pathology of MI. Teriflunomide (TERI), an orally active Dihydroorotate Dehydrogenase inhibitor, inhibits de novo pyrimidine synthesis. It decreases production of inflammatory cytokines and suppresses the activity and proliferation of activated lymphocytes. Hypothesis: TERI, on account of its potent anti-inflammatory activity may attenuate Isoproterenol induced cardiac injury in rats. Thus, we aimed to investigate the cardio-protective effect of Teriflunomide in isoproterenol (Iso) induced myocardial infarction. Design and method: To induce myocardial infarction in rats, we administered 2 doses of Isoproterenol (85 mg/kg/day, s.c.) on days 13th and 14th, at an interval of 24 hours. Male albino Wistar rats were divided into 5 groups (n = 6); namely normal control, isoproterenol control, Teriflunomide groups to receive saline, isoproterenol, or Teriflunomide (1, 3 or 5 mg/kg/day, p.o.) for 14 days. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Blood sample was collected via cardiac puncture, heart was excised and preserved for analysis of biochemical, histopathological and ultrastructural studies. Results: Isoproterenol administration to rats resulted in induction of MI with impairment of hemodynamic parameters. Teriflunomide pretreatment showed significantly improved hemodynamic (systolic, diastolic and mean blood pressures) and cardiac function parameters (normalized ± LV dP/dt and LVEDP) with reduction in the levels of cardiac injury markers (CK-MB, LDH). Further, Teriflunomide significantly reduced oxidative stress (enhanced levels of SOD, GSH, decreased MDA levels) and inflammation (reduced levels of TNF-alpha, IL-6), led to inhibition of active JNK and p38 proteins and activation of ERK1/2, a pro-survival kinase. Furthermore, it also ameliorated apoptosis by reducing the expression of pro-apoptotic proteins (Bax and Caspase-3) and increased expression of Bcl-2, an anti-apoptotic marker. In addition, pretreatment with Teriflunomide preserved morphological and ultra-structural architecture of the myocardium as seen by H & E staining and electron microscopy. Conclusions: Teriflunomide at 1 mg/kg offered cardio-protection by improving hemodynamic profile, oxidative stress profile, reduced inflammation, normalization of myocardial architecture.

4-OCTYL ITACONATE ATTENUATES ISOPROTERENOL INDUCED MYOCARDIAL DAMAGE VIA NLRP3 INFLAMMASOME PATHWAY, NRF-2/HO-1 AND MAPK PATHWAY IN AN EXPERIMENTAL MODEL

Objective: Myocardial infarction (MI) is the major cause of morbidity and mortality worldwide. According to the World Health Organisation, more than 9 million deaths occurred due to ischemic heart disease worldwide in 2016. 4-octyl itaconate (4-OI) is a cell permeable derivative of itaconate with potent anti-oxidative, anti-inflammatory and anti-fibrotic properties. Studies have shown that 4-OI inhibits pro-inflammatory cytokines (IL6, IL1beta, TNF alpha) and activates the anti-oxidant Nrf-2/HO-1 pathway. The aim of the study was to investigate the cardio-protective effect of 4-OI in experimental model of Isoproterenol induced myocardial damage. Design and method: Adult male albino wistar rats were used in the study. They were randomly divided to five groups i.e., normal control group, isoproterenol control group, 4-OI group (2.5, 5 or 10 mg/kg) for 14 days and 4-OI perse group. On the 15th day, rats were anaesthetized and right coronary artery was cannulated to record hemodynamic parameters. Following this, blood was withdrawn using cardiac puncture, heart was excised and preserved for analysis of biochemical, histopathological and molecular pathway studies. Results: Isoproterenol administration to rats resulted in induction of Myocardial damage as shown by impairment in hemodynamic parameters, left ventricular dysfunction and raised cardiac injury markers. Treatment with 4-OI significantly improved hemodynamic and cardiac injury markers (CKMB, LDH). Further, 4OI significantly reduced oxidative stress (enhanced levels of SOD, GSH, decreased MDA levels) and inflammation (reduced levels of TNF alpha, IL-6, IL-1beta and NLRP3). Further it activated the Nrf-2-HO-1 pathway while inhibits the inflammatory NFKB pathway. Apart from this, it also ameliorated apoptosis by decreasing the expression of Bax, caspase-3 and increasing the expression of anti-apoptotic Bcl-2. It also inhibited inflammatory MAPK proteins (JNK, phospho JNK, P38, phospho P38) while enhancing the expression of pro-survival kinases ERK1/2, and Phospho ERK1/ 2. Conclusions: Oral administration of 4-OI at a dose of 10 mg/kg ameliorated the severity of isoprotorenol-induced cardio-toxicity in rats via NLRP-3 inflammasome pathway, MAPK and Nrf-2/HO1 pathway and by maintaining morphological structure of heart tissue and oxidative stress profile along with reduced inflammation and apoptosis.

Dual oxidative stress and fatty acid profile impacts in Paracentrotus lividus exposed to lambda-cyhalothrin: biochemical and histopathological responses.

Lambda-cyhalothrin (λ-cyh) is a potential pyrethroid insecticide widely used in pest control. The presence of pyrethroids in the aquatic ecosystem may induce adverse effects on non-target organisms such as the sea urchin. This study was conducted to assess the toxic effects of λ-cyh on the fatty acid profiles, redox status, and histopathological aspects of Paracentrotus lividus gonads following exposure to three concentrations of λ-cyh (100, 250 and 500µg/L) for 72h. The results showed a significant decrease in saturated fatty acid (SFAs) with an increase in monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) levels in λ-cyh treated sea urchins. The highest levels in PUFAs were recorded in the eicosapentaenoic acids (C20:5n-3), docosahexaenoic acids (C22:6n-3) and arachidonic acids (C20:4n-6) levels. The λ-cyh intoxication promoted oxidative stress with an increase in hydrogen peroxide (H2O2), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels. Furthermore, the enzymatic activities and non-enzymatic antioxidants levels were enhanced in all exposed sea urchins, while the vitamin C levels were decreased in 100 and 500µg/L treated groups. Our biochemical results have been confirmed by the histopathological observations. Collectively, our findings offered valuable insights into the importance of assessing fatty acids' profiles as a relevant tool in aquatic ecotoxicological studies.

Nephroprotective effect of milkfish, patin, and snakehead fish oil by suppressing inflammation and oxidative stress in diabetic rats

Diabetic nephropathy (DN) has been linked to a number of long-term problems caused by diabetes mellitus. Inflammatory and oxidative stress pathways contribute to DN development and progression. Many studies have shown the preventive advantages of diets rich in substances like anti-inflammatory and antioxidant elements like omega-3 fatty acids (n-3 FA) in preventing DN. Milkfish (Chanos chanos F.), patin (Pangasius micronema Blkr.), and snakehead fish (Chana striata Bloch) are types of fish oils that are known to contain n-3 FA. This study aims to prove the nephroprotective effect of the three types of fish oil in a rat model of diabetes mellitus. Thirty male rats were used in this study. The animals were randomly divided into six groups (n = 5): the non-diabetic group, the diabetes mellitus group, the diabetic with 150 mg/kg metformin orally group, the diabetic with 1000 mg/kg milkfish oil orally group, the diabetic with 1000 mg/kg patin fish oil orally group, and the diabetic with 1000 mg/kg snakehead fish oil orally group. Diabetes models were induced using 65 mg/kg streptozotocin and 230 mg/kg nicotinamide intraperitoneally. The test was carried out for 8 weeks, followed by the observation of the biochemical profiles of blood, urine, oxidative stress, and the immunohistochemistry of the kidneys. A normally and homogeneously distributed test followed by a one-way analysis of variance (ANOVA) and the LSD post hoc test were used to look at the data. At p≤0.05, the data was considered statistically significant. The results showed that serum creatinine levels did not differ significantly after the administration of milkfish, catfish, and snakehead fish oil for 8 weeks (p≥0.05). Different results were shown where the levels of serum BUN, uric acid, urine urea, and microalbumin urine were significantly different after administration of the three types of fish oil (p≤0.05). The same results were shown in oxidative stress (superoxide dismutase, glutathione, and malondialdehyde) and inflammation (interleukin-6 and tumor necrosis factor-α) profiles (p≤0.05). The conclusion is that milkfish, patin, and snakehead fish oils have moderate nephroprotection by suppressing inflammation and oxidative stress.

Effects of Ubiquinone on Oxidant and Antioxidant Status in Hepatocellular Carcinoma Cell Line

Background and Aims: The concomitant use of antioxidants during chemotherapy is controversial. It is unknown whether antioxidants increase or decrease the effectiveness of anticancer drugs. Therefore, the present study aimed to investigate ubiquinone's cytotoxic and antioxidant effects on the HepG2 cell line.
 Materials and Methods: The HepG2 cell line was chosen as an experimental model for hepatocellular carcinoma in this study. The cytotoxic effect of ubiquinone was assessed as a function of time and concentration using the colorimetric MTT assay. The half-maximal inhibitory concentration (IC50) was determined to assess the cytotoxic effects of different ubiquinone concentrations. The protective impacts of ubiquinone on HepG2 cells were evaluated by assessing the oxidative stress profile.
 Results: The MTT showed that the IC50 after treatment with ubiquinone was 350 and 335 μM at 24 and 48 hours, respectively. Evaluation of redox homeostasis in HepG2 cells using three doses of ubiquinone, including IC50 and one dose higher and one dose lower than IC50, showed a decrease in oxidative stress and an increase in the antioxidant capacity of HepG2 cells in a dose-dependent manner (p < 0.01). An increase in redox hemostasis decreased the viability of HepG2 cells.
 Conclusion: Our results showed ubiquinone could reduce cancer cell survival by interfering in redox oxidative-redox status. Therefore, ubiquinone can be used as an antioxidant supplement along with chemotherapy drugs.

Attenuating effects of selenium and zinc against hexavalent chromium-induced oxidative stress, hormonal instability, and placenta damage in preimplanted rats.

As a toxic metal, hexavalent chromium (CrVI) has effects on both the reproductive and endocrine systems. This study aimed to evaluate the protective effects of selenium (Se) and zinc (Zn) against the toxicity of chromium on the placenta in pregnant Wistar albino rats. Thirty pregnant Wistar rats were divided into control and four treated groups, receiving subcutaneously (s.c) on the 3rd day of pregnancy, K2Cr2O7 (10mg/kg body weight (bw)) alone, or in association with Se (0.3mg/kg bw), ZnCl2 (20mg/kg bw), or both of them simultaneously. Plasma steroid hormones, placenta histoarchitecture, oxidative stress profile, and developmental parameters were investigated. These results showed that K2Cr2O7 exposure induced a significant increase in the levels of both plasma estradiol (E2) and placenta malondialdehyde (MDA), the number of fetal resorptions, and percent of post-implantation loss. On the other hand, K2Cr2O7 significantly reduced developmental parameters, maternal body and placenta weight, and plasma progesterone (P) and chorionic gonadotropin hormone (β HCG) levels. However, K2Cr2O7 significantly decreased the placenta activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH), and nonprotein sulfhydryl (NPSH). These changes have been reinforced by histopathological evaluation of the placenta. Se and/or ZnCl2 supplementation provoked a significant improvement in most indices. These results suggest that the co-treatment with Se or ZnCl2 strongly opposes the placenta cytotoxicity induced by K2Cr2O7 through its antioxidant action.

Comparative Effect of the Active Substance of Thyme with N-Acetyl Cysteine on Hematological Parameters and Histopathological Changes of Bone Marrow and Liver in Rat Models of Acetaminophen Toxicity.

Acetaminophen has always been at the center of attention as a non-steroidal anti-inflammatory drug, which is generally associated with the serious side effects on liver and the hematological parameters. This study aimed to compare the effect of N-acetyl cysteine (NAC) and thyme extract on rat models of acetaminophen-induced toxicity. The present experimental study was conducted on 48 Wistar rats randomized into six groups, including the control group (no treatment); the Ac group (470 mg/kg of acetaminophen); the Ac + 100Ex, Ac + 200Ex, and Ac + 400Ex groups (acetaminophen + thyme extract at doses of 100, 200, 400 mg/kg); and Ac + NA group (acetaminophen + NAC). After weighing, a blood sample was taken from heart at the end of the period. The measured parameters were hematological, liver biochemical, and oxidative stress profiles. A part of the liver tissue was also fixed for the pathological examinations. The bone marrow was aspirated to check for cellular changes as well. The lowest mean of the final weight and liver weight to body weight ratio was observed in the Ac group. Weight loss was compensated in Ac + NA and Ac + 200Ex groups (P = 0.035). White blood cell (WBC), red blood cell (RBC), Hemoglobin (Hgb), and Hematocrit (HCT) in Ac and Ac + 400Ex groups showed significant differences from those of the other test groups (P < 0.001). Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) enzymes in Ac + 200Ex and Ac + NA groups showed a significant decrease compared to those of the other treatment groups (P = 0.043). Total antioxidant capacity (TAC) and glutathione peroxidase (GPx) had the lowest levels in Ac and Ac + 400Ex groups, while malondialdehyde (MDA) had the highest content. In this regard, the liver histopathological indices (necrosis, hyperemia, and hemorrhage) in the Ac + 200Ex and Ac + NA groups reached their lowest grades in the treatment groups. The mean number of erythroid and myeloid cells in the Ac group reached the lowest (17.40 ± 3.48). The microscopic appearance of the bone marrow cells was different from normocytosis in the control group to hypocytosis in the Ac and Ac + 400Ex groups. Thymol, as an effective ingredient in thyme extract at a dose of 200 mg/kg compared to NAC, had a unique effect on reducing bone marrow and liver cell-tissue changes due to the acetaminophen toxicity.

Hypoxia Enhances Oxidative Stress in Neutrophils from ZZ Alpha-1 Antitrypsin Deficiency Patients.

Alpha-1 antitrypsin deficiency (AATD) is a neutrophilic inflammatory disorder that may result in local hypoxia, reactive oxygen and nitrogen species (ROS/RNS) production, and increased damage in adjacent tissues. This study aims to determine the impact of hypoxia on neutrophil oxidative stress profile in AATD patients. Neutrophils were isolated from AATD patients and control volunteers and exposed to hypoxia (1% O2 for 4 h), ROS/RNS, mitochondrial parameters, and non-enzymatic antioxidant defenses measured by flow cytometry. The expression of enzymatic antioxidant defenses was determined by qRT-PCR. Our results indicate that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes catalase, superoxide dismutase, and glutathione reductase. Likewise, our results show a decrease in mitochondrial membrane potential, indicating that this organelle could be involved in the production of the reactive species observed. No decrease in glutathione and thiol levels were observed. The accumulation of substances with high oxidative capacity would explain the greater oxidative damage observed in proteins and lipids. In conclusion, our results indicate that, compared to MM control individuals, ZZ-AATD neutrophils show increased ROS/RNS production under hypoxic conditions opening a new rationale for using antioxidant therapies to treat the disease.

Pomegranate Seeds and Peel Ethanolic Extracts Anticancer Potentials and Related Genetic, Histological, Immunohistochemical, Apoptotic and Oxidative Stress Profiles: In vitro Study.

Owing to their great quantity of hydrolyzable anthocyanins and tannins, the peel and seeds of pomegranate are edible and possess potent anti-oxidant and anti-inflammatory characteristics. This work aims to trace the pomegranate seed and peel ethanolic extracts' anticancer activity against liver cancer cell line, namely HepG2 and related histopathological, immunohistochemical, genetic and oxidative stress profile. In vitro study for both seed and peel extract showed the prevalence of phenols, polyphenols and acids, those have anti-proliferative potential against liver cancer cell line (HepG2) with 50% inhibitory concentration (IC50) of seed significantly reduced that of peel. Toxicity of test extracts was concentration dependent and accompanied with cell cycle arrest and cell death at theG0/G1 and S phases but not at the G2/M phase. Cell arrest was supplemented with raised ROS, MDA and decreased SOD, GSH and Catalase. Apoptosis-related genes showed significant up-expression of pro-apoptotic gene (P53), Cy-C, Bax, and casp-3 and down expression of anti-apoptotic gene (Bcl-2). Also, Casp-3 and P53 proteins were substantially expressed under the effect of test extracts. Histopathological study demonstrated that the untreated cells (control group) were regular cells with nuclear pleomorphism and hyperchromatic nuclei, while seed and peel extracts-treated cells showed necrosis, mixed euchromatin and heterochromatin, intra-nuclear eosinophilic structures, burst cell membranes, and the shrunken apoptotic cells with nuclear membranes and irregular cells. Finally, PCNA gene detected by immunohistochemistry was down regulated significantly under the effect of seed extract treatment than in case of cell medication with peel extract.

The Histopathological and Oxidative Stress Profiles in Japanese Quails (Coturnix japonica) Induced by Dietary Lead.

In their native habitat, avians are exposed to external toxicity factors, the most prominent of which are chemical lead compounds that threaten human and animal health. The goal of this investigation was to estimate the adverse effects of lead acetate (Pb(CH3COO)2 (H2O)3) on the health status of Japanese quail (Coturnix japonica). 18 adult male Japanese quails (Coturnix coturnix japonica) were employed in this investigation. After two weeks of acclimatization, the birds were randomly divided into three groups: the control group received no Pb+2, the Low Dose Group received 50 mg/kg of Pb+2 as lead acetate Pb(CH3COO)2 (H2O)3 in the diet, and the High Dose Group received 100 mg/kg of Pb+2 as lead acetate Pb(CH3COO)2(H2O)3 in the diet, for 30 days. Results showed that the Pb bioaccumulation was recorded at the highest values in the liver compared with the kidney, and as expected, the ranges of the lead accumulation were significantly higher in the animals who received 100 mg/kg Pb compared with animals who received 50 mg/kg Pb and the control group. In the high dose group, serum content showed significantly increased levels (P≤0.05) of aminotransferase enzymes (ALT and AST ), glucose, creatinine, and uric acid levels compared to other groups, while antioxidant enzymes (CAT, GSH, and GSH-PX) levels in the liver and kidney were significantly reduced (P≤0.05). The results showed that the MDA appeared to be significantly increasing (P≤0.05) in the high dose group compared to the other groups. Compared to the low dose and control groups, the high dosage group produced substantial histological abnormalities in the liver and kidney.

Experimental and theoretical insights about the effect of some newly designed azomethine group‐contained macroheterocycles on oxidative stress and DNA repair gene profiles in neuroblastoma cell lines

We report herein the synthesis of new azomethine group containing forty-, sixty-eight- and seventy-two-membered macroheterocyclic compounds and the investigation of their activity against the neuroblastoma cell line. The synthesis of targeted compounds was done by condensation of dialdehydes with polyamines and their structures were investigated by 1H and 13C NMR and MALDI MS methods. Anticancer activity of these newly synthesized molecules was studied in the neuroblastoma (SH-SY5Y) cell line at eight different concentrations (1–100 µg/ml) for 24 h, 48 ​​hrs and 72 h by MTT method. In addition to it, oxidative stress (GPX1, PRDX1, CAT, SOD1, NQO1) and DNA repair (ATR, ERCC1, CDKN1A, PRKDC) gene profiles were also investigated by RT-PCR method. It was found that all synthesized compounds showed the highest activity after 72 h of incubation. PRDX1 gene expression in the case of all investigated compounds was found to be higher than the control group, whereas ABCB1 (MDR) gene expression increased only in the case of molecule 1. Results also demonstrate that the expression levels of GPX and SOD1 genes were high in the case of molecule 2, whereas molecule 1 manifested low expression levels of ERCC1, ATR, CDKN1A, PRKDC, GPX1, ABCB1(MDR), CAT, SOD1 and NQO1 genes. Along with experimental studies, theoretical studies were also carried out. The String v11 program was used to determine the interaction of proteins involved in oxidative stress and DNA repair mechanisms with other proteins. The results of the molecular docking analysis were found to be in good agreement with the experiments.

Influence of goat management systems on hematological, oxidative stress profiles, and parasitic gastrointestinal infection.

Good management in goats is known for good quality health and increasing productivity. The physiological change studies in goats are limited despite some existing studies on the relationship of various patterns to growth rates. This study aimed to determine the hematological parameters, oxidative stress, and parasitic infection in three management systems in Thai native goats. A total of 18 male goats were randomly assigned to the three systems: The free-range model (FREE), the semi-intensive model (SEMI), and the kept-in-a-cage model (BARN) for 35 days. Blood, fecal sampling, and weight data were collected and monitored every 5 days for analysis. No statistical differences were found in the FREE and SEMI groups, but significance was observed in the BARN group. The body weight of the goats gradually reduced from 13.0 ± 2.44 kg to 10.18 ± 2.61 kg (mean ± standard deviation). In contrast, the significantly increasing red blood cells, packed-cell volume, white blood cells, neutrophil-to-lymphocyte (N/L) ratio, cortisol hormone, and antioxidation profiles were observed to be higher in BARN than in FREE and SEMI groups. The intensity of the parasite eggs was remarkably significant. It was observed in the BARN group between the beginning and end of the experiment (supported by a high level of eosinophils). These data can be applied for the realistic evaluation and improvement of management practices, especially fully restrained management (BARN) for monitoring the health status of goats.

Studying the actions of sage and thymoquinone combination on metabolic syndrome induced by high-fat diet in rats.

High-fat diet is one of the most imperative risk factors for cardiovascular disorders. Thymoquinone (TQ) is one of the active pharmacological components of Nigella sativa (black cumin). Salvia officinalis L. (sage) has been demonstrated to have diverse pharmacological actions. The main objective of this study was to determine the effects of sage and TQ combination on hyperglycemia, oxidative stress, blood pressure, and lipid profile in rats fed with a high-fat diet (HFD). Wistar male rats were divided into five groups; normal diet (ND) and HFD, in which rats were fed with a normal diet or HFD for 10 weeks, respectively. In HFD + sage group, animals were administered sage essential oil (0.052 ml/kg) orally along with HFD. In HFD + TQ group, rats were administered TQ (50 mg/kg) orally with HFD. In HF + sage + TQ group, animals received sage + TQ along with HFD. Blood glucose (BGL) and Fast serum insulin (FSI) levels, oral glucose tolerance test, blood pressure, liver function tests, plasma, and hepatic oxidative stress markers, antioxidant enzymes, and glutathione content, and lipid profile were measured. Sage and TQ combination decreased the final body weight, weight gain, BGL, FSI, and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). The combination also lowered systolic and diastolic arterial pressures and liver function enzymes. The combination deterred lipid peroxidation, advanced protein oxidation product, and nitric oxide amplification, as well as restoring the superoxide dismutase, catalase activities, and glutathione content in plasma and hepatic tissue. Sage and TQ combination reduced the plasma total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels and amplified high-density lipoprotein (HDL). The results of the current study verified that sage essential oil, together with TQ exhibited hypoglycemic, hypolipidemic, and antioxidant actions and thus could be a valuable addition to diabetes management.

Repression of the aryl-hydrocarbon receptor prevents oxidative stress and ferroptosis of intestinal intraepithelial lymphocytes

The aryl-hydrocarbon receptor (AHR) is a ligand-activated transcription factor that buoys intestinal immune responses. AHR induces its own negative regulator, the AHR repressor (AHRR). Here, we show that AHRR is vital to sustaining intestinal intraepithelial lymphocytes (IELs). AHRR deficiency reduced IEL representation in a cell-intrinsic fashion. Single-cell RNA sequencing revealed an oxidative stress profile in Ahrr-/- IELs. AHRR deficiency unleashed AHR-induced expression of CYP1A1, a monooxygenase that generates reactive oxygen species, increasing redox imbalance, lipid peroxidation, and ferroptosis in Ahrr-/- IELs. Dietary supplementation with selenium or vitamin E to restore redox homeostasis rescued Ahrr-/- IELs. Loss of IELs in Ahrr-/- mice caused susceptibility to Clostridium difficile infection and dextran sodium-sulfate-induced colitis. Inflamed tissue of inflammatory bowel disease patients showed reduced Ahrr expression that may contribute to disease. We conclude that AHR signaling must be tightly regulated to prevent oxidative stress and ferroptosis of IELs and to preserve intestinal immune responses.

Low oxygen tension affects proliferation and senescence of caprine bone marrow mesenchymal stem cells in in vitro culture condition

The culture system of bone marrow mesenchymal stem cells (bmMSCs) in the normoxic environment does not imitate the hypoxic milieu of typical biological conditions, thus hypoxic culture conditions may improve survival, and growth attributes of bmMSCs during in vitro culture. Therefore, the present study was conducted at ICAR-CIRG, Makhdoom during year 2020 with the objective to investigate the changes in biological characteristics of cultured caprine bmMSCs (cbmMSCs) including the cellular senescence, survival, rate of proliferation, immuno-phenotypic characteristics, and gene expression pattern in a normal and hypoxic microenvironment condition. For this, cbmMSCs isolated from bone marrow collected from iliac crest were enriched and grown under either hypoxic (5% O2) or normoxic (20% O2) conditions. Thereafter, the outcome of hypoxic (5% O2) culturing of cbmMSCs on growth characteristics, proliferation, senescence, and expression profile of important stemness-associated (OCT-4) and oxidative stress [glutathione peroxidase (GPx1) and copper-zinc superoxide dismutase (CuZnSOD)] marker genes was evaluated. cbmMSCs cultivated in hypoxic conditions showed higher proliferation and decreased population doubling time and senescence-associated β-GAL expression; however, the immune-phenotypic characteristics of the cells remain unchanged. Furthermore, the culture of cbmMSCs in hypoxia increased the expression of OCT-4, GPx1, and CuZnSOD, compared with the cells grown under normoxia. In conclusion, the culture condition with low O2 level improved the growth characteristics and proliferation of cbmMSCs. These outcomes would provide information to formulate strategies for the collection and efficient in vitro expansion of bmMSCs from goats and other farm animals before their downstream applications.

The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3',4'-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease.

The aim of this study was to analyze the possible nephroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7-7.8% reduction in DHPG-treated rats), as well as 38-56% reduction in urinary protein excretion and 22-46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson's coefficient 0.68-0.74), antinitrosative (Pearson's coefficient 0.83), and prostacyclin production regulator (Pearson's coefficient 0.75) effects.

Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model.

Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.